The present invention relates to a process for removing impurities from a racemic mixture of cis isomers of a compound of Formula I, cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol, (hereinafter “racemic lasofoxifene” or “racemate”).

This invention also relates to a purified racemic lasofoxifene, cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol, (hereinafter “purified racemic lasofoxifene” or “purified racemate”), and purified lasofoxifene D-tartrate, (−)cis-6(S)-phenyl-5(R)-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol D-tartrate, which is useful as an estrogen agonist/antagonist, also known as a selective estrogen receptor modulator (“SERM”). Racemic lasofoxifene is an intermediate in the syntheses of lasofoxifene D-tartrate, having the following structure:

Lasofoxifene, lasofoxifene D-tartrate, its racemate and processes for the preparation thereof, are disclosed in commonly assigned U.S. Pat. No. 5,552,412, issued Sep. 3, 1996, and U.S. Pat. No. 5,948,809, issued Sep. 7, 1999. The text of these patents and all other references cited in this specification are hereby incorporated by reference in their entirety.
Typically, drug substances preferably contain less than 0.2%. impurities, most preferably less than 0.1% impurities. During the scale-up process for commercial production of lasofoxifene D-tartrate, however, it was determined that the resulting lasofoxifene D-tartrate compound contained undesirable impurities greater than 0.2%. It was also determined that purification of lasofoxifene D-tartrate to less than 0.1% impurities was not commercially feasible at the proposed scale-up. Consequently, there was a need to obtain an intermediate of Lasofoxifene D-tartrate, having a purity of less than 0.1% impurities. The process described within the instant invention resolves this issue.